Blocking lncRNA HCG18 re-sensitizes Taxol resistant lung cancer cells to Taxol through modulating the miR-34a-5p/HDAC1 axis.

Lung cancer is one of the most frequently diagnosed cancers worldwide, associated with a poor survival rate. Taxol (Paclitaxel) is commonly used as a chemotherapeutic treatment for advanced lung cancers. While Taxol has improved clinical outcomes for lung cancer patients, a significant number of them develop resistance to Taxol, resulting in treatment failure. The role of the long noncoding RNA HCG18 in lung cancer and Taxol resistance has not yet been fully understood. To investigate this, we examined the expression of HCG18 and miR-34a-5p in lung tumors and normal lung tissues using qRT-PCR. We also assessed Taxol resistance through cell viability and apoptosis assays. Through the starBase online service, we analyzed the interactions between lncRNA and mRNA as well as miRNA and mRNA. We further validated the association between lncRNA and miRNA through luciferase and RNA pull-down assays. Our findings demonstrated that HCG18 was significantly upregulated in lung cancer tissues compared to normal lung tissues. Silencing HCG18 increased the sensitivity of lung cancer cells to Taxol. Additionally, our study established a Taxol-resistant cell line and observed a substantial upregulation of HCG18 in Taxol-resistant lung cancer cells. Bioinformatic analysis predicted that HCG18 could bind to miR-34a-5p, forming a competing endogenous RNA network, which was confirmed through luciferase assay. We found that miR-34a-5p was downregulated in lung cancer tissues and negatively correlated with Taxol resistance, as it directly bound to the 3'UTR region of HDAC1. Further results showed that inhibition of HCG18 significantly increased miR-34a-5p expression and sensitized lung cancer cells to Taxol. This sensitization could be reversed by inhibiting miR-34a-5p. Finally, we demonstrated in a xenograft mouse model that inhibition of HCG18 sensitized Taxol-resistant lung cancer cells to Taxol treatment by modulating the miR-34a-5p-HDAC1 axis. In conclusion, our in vitro and in vivo results uncover a novel molecular mechanism by which HCG18 promotes Taxol resistance through modulation of the miR-34a-5p/HDAC1 axis. These findings contribute to the diagnosis and treatment of chemo-resistant lung cancer.

Identification of Hsp20 gene family in Malus domestica and functional characterization of Hsp20 class I gene MdHsp18.2b.

Heat shock protein 20 (Hsp20) is a small molecule heat shock protein that plays an important role in plant growth, development, and stress resistance. Little is known about the function of Hsp20 family genes in apple (Malus domestica). Here, we performed a genome-wide analysis of the apple Hsp20 gene family, and a total of 49 Hsp20s genes were identified from the apple genome. Phylogenetic analysis revealed that the 49 genes were divided into 11 subfamilies, and MdHsp18.2b, a member located in the CI branch, was selected as a representative member for functional characterization. Treatment with NaCl and Botryosphaeria dothidea (B. dothidea), the causal agent of apple ring rot disease, significantly induced MdHsp18.2b transcription level. Further analysis revealed that overexpressing MdHsp18.2b reduced the resistance to salt stress but enhanced the resistance to B. dothidea infection in apple calli. Moreover, MdHsp18.2b positively regulated anthocyanin accumulation in apple calli. Physiology assays revealed that MdHsp18.2b promoted H2O2 production, even in the absence of stress factors, which might contribute to its functions in response to NaCl and B. dothidea infection. Hsps usually function as homo- or heterooligomers, and we found that MdHsp18.2b could form a heterodimer with MdHsp17.9a and MdHsp17.5, two members from the same branch with MdHsp18.2b in the phylogenetic tree. Therefore, we identified 49 Hsp20s genes from the apple genome and found that MdHsp18.2b was involved in regulating plant resistance to salt stress and B. dothidea infection, as well as in regulating anthocyanin accumulation in apple calli.

Modulation of Nucleation and Growth Kinetics of Perovskite Nanocrystals Enables Efficient and Spectrally Stable Pure-Red Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) based on CsPb(Br/I)3 nanocrystals (NCs) usually suffer from severe spectral instability under operating voltage due to the poor-quality PeNCs. Herein, zeolite was utilized to prepare high-quality CsPb(Br/I)3 NCs via promoting the homogeneous nucleation and growth and suppressing the Ostwald ripening of PeNCs. In addition, the decomposed zeolite interacted strongly with PeNCs through Pb-O bonds and hydrogen bonds, which inhibited the formation of defects and suppressed halide ion migration, leading to an improved photoluminescence quantum yield (PLQY) and enhanced stability of PeNCs. Moreover, the strong binding affinity of decomposed zeolite to PeNCs contributed to the formation of homogeneous perovskite films with high PLQY. As a result, pure-red PeLEDs with Commission International de I'Eclairage (CIE) coordinates of (0.705, 0.291) were fabricated, approaching the Rec. 2020 red primary color. The devices achieved a peak external quantum efficiency of 23.0% and outstanding spectral stability.

CircNOP14 increases the radiosensitivity of hepatocellular carcinoma via inhibition of Ku70-dependent DNA damage repair.

Circular RNAs (circRNAs) are profoundly affected in hepatocellular carcinoma (HCC) through various pathways. However, the role of circRNAs in the radiosensitivity of HCC cells is yet to be explored. In this study, we identified a circRNA-hsa_circ_0006737 (circNOP14) involved in the radiosensitivity of HCC. We found that circNOP14 increased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified Ku70 as a novel and robust interacting protein of circNOP14. Mechanistically, circNOP14 interacts with Ku70 and prevents its nuclear translocation, thereby increasing irradiation-induced DNA damage. Therefore, our findings may provide a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

NCF4 regulates antigen presentation of cysteine peptides by intracellular oxidative response and restricts activation of autoreactive and arthritogenic T cells.

Autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematous, are regulated by polymorphisms in genes contributing to the NOX2 complex. Mutations in both Ncf1 and Ncf4 affect development of arthritis in experimental models of RA, but the different regulatory pathways mediated by NOX2-derived reactive oxygen species (ROS) have not yet been clarified. Here we address the possibility that intracellular ROS, regulated by the NCF4 protein (earlier often denoted p40phox) which interacts with endosomal membranes, could play an important role in the oxidation of cysteine peptides in mononuclear phagocytic cells, thereby regulating antigen presentation and activation of arthritogenic T cells. To study the role of NCF4 we used mice with an amino acid replacing mutation (NCF4R58A), which is known to affect interaction with endosomal membranes, leading to decreased intracellular ROS production. To study the impact of NCF4 on T cell activation, we used the glucose phosphate isomerase peptide GPI325-339, which contains two cysteine residues (325-339c-c). Macrophages from mice with the NCF458A mutation efficiently presented the peptide when the two cysteines were intact and not crosslinked, leading to a strong arthritogenic T cell response. T cell priming occurred in the draining lymph nodes (LNs) within 8 days after immunization. Clodronate treatment, which depletes antigen-presenting mononuclear phagocytes, ameliorated arthritis severity, whereas treatment with FYT720, which traps activated T cells in LNs, prohibited arthritis. We conclude that NCF4-dependent intracellular ROS maintains cysteine peptides in an oxidized crosslinked state, which prevents presentation of peptides recognized by non-tolerized T cells and thereby protects against autoimmune arthritis.

Functions of Phytochrome Interacting Factors (PIFs) in Adapting Plants to Biotic and Abiotic Stresses.

Plants possess the remarkable ability to sense detrimental environmental stimuli and launch sophisticated signal cascades that culminate in tailored responses to facilitate their survival, and transcription factors (TFs) are closely involved in these processes. Phytochrome interacting factors (PIFs) are among these TFs and belong to the basic helix-loop-helix family. PIFs are initially identified and have now been well established as core regulators of phytochrome-associated pathways in response to the light signal in plants. However, a growing body of evidence has unraveled that PIFs also play a crucial role in adapting plants to various biological and environmental pressures. In this review, we summarize and highlight that PIFs function as a signal hub that integrates multiple environmental cues, including abiotic (i.e., drought, temperature, and salinity) and biotic stresses to optimize plant growth and development. PIFs not only function as transcription factors to reprogram the expression of related genes, but also interact with various factors to adapt plants to harsh environments. This review will contribute to understanding the multifaceted functions of PIFs in response to different stress conditions, which will shed light on efforts to further dissect the novel functions of PIFs, especially in adaption to detrimental environments for a better survival of plants.

Multi-Species Surface Reconstruction for High-Efficiency Perovskite Nanocrystal Light-Emitting Diodes.

Although colloidal perovskite nanocrystal (PNC) solution has exhibited near-unity photoluminescence quantum yield (PLQY), the luminance would be severely quenched when the PNC solution is assembled into thin films due to the agglomeration and fusion of NCs caused by the exfoliation of surface ligands and non-radiative Förster resonance energy transfer (FRET) from small to large particle sizes, which seriously affected the performances of light-emitting diodes (LEDs). Here, we used Guanidine thiocyanate (GASCN) and Sodium thiocyanate (NaSCN) to achieve effective CsPbI3 PNC surface reconstruction. Due to the strong coordination ability of these small molecules with the anions and cations on the surface of the PNCs, they can provide strong surface protection against PNC fusion during centrifugal purification process and repair the surface defects of PNCs, so that the original uniform size distribution of PNCs can be maintained and FRET between close-packed PNC films is effectively suppressed, which allows the emission characteristics of the films to be preserved. As a result, highly oriented, smooth and nearly defect-free high-quality PNC thin films are obtained, with PLQY as high as 95.1 %, far exceeding that of the original film, and corresponding LEDs exhibit a maximum external quantum efficiency of 24.5 %.

Plant disease resistance outputs regulated by AP2/ERF transcription factor family.

Plants have evolved a complex and elaborate signaling network to respond appropriately to the pathogen invasion by regulating expression of defensive genes through certain transcription factors. The APETALA2/ethylene response factor (AP2/ERF) family members have been determined as key regulators in growth, development, and stress responses in plants. Moreover, a growing body of evidence has demonstrated the critical roles of AP2/ERFs in plant disease resistance. In this review, we describe recent advances for the function of AP2/ERFs in defense responses against microbial pathogens. We summarize that AP2/ERFs are involved in plant disease resistance by acting downstream of mitogen activated protein kinase (MAPK) cascades, and regulating expression of genes associated with hormonal signaling pathways, biosynthesis of secondary metabolites, and formation of physical barriers in an MAPK-dependent or -independent manner. The present review provides a multidimensional perspective on the functions of AP2/ERFs in plant disease resistance, which will facilitate the understanding and future investigation on the roles of AP2/ERFs in plant immunity.

High-Performance Blue Perovskite Light-Emitting Diodes Enabled by Synergistic Effect of Additives.

While quasi-two-dimensional (quasi-2D) perovskites have good properties of cascade energy transfer, high exciton binding energy, and high quantum efficiency, which will benefit high-efficiency blue PeLEDs, inefficient domain distribution management and unbalanced carrier transport impede device performance improvement. Herein, (2-(9H-carbazol-9-yl)ethyl)phosphonic acid (2PACz) and methyl 2-aminopyridine-4-carboxylate (MAC) were simultaneously introduced to a blue quasi-2D perovskite film. Relying on the synergistic effect of 2PACz and MAC, it not only modulates the phase distribution inhibiting the n = 2 phase but also greatly improves the electrical property of the quasi-2D perovskite film. As a result, the as-modified blue quasi-2D PeLED demonstrated an external quantum efficiency (EQE) of 17.08% and a luminance of 10142 cd m-2. This study exemplifies the synergistic effect among dual additives and offers a new effective additive strategy modulating phase distribution and building balanced carrier transport, which paves the way for the fabrication of highly efficient blue PeLEDs.

Association between serum multi-protein biomarker profile and real-world disability in multiple sclerosis.

Few studies examined blood biomarkers informative of patient-reported outcome (PRO) of disability in people with multiple sclerosis (MS). We examined the associations between serum multi-protein biomarker profiles and patient-reported MS disability. In this cross-sectional study (2017-2020), adults with diagnosis of MS (or precursors) from two independent clinic-based cohorts were divided into a training and test set. For predictors, we examined seven clinical factors (age at sample collection, sex, race/ethnicity, disease subtype, disease duration, disease-modifying therapy [DMT], and time interval between sample collection and closest PRO assessment) and 19 serum protein biomarkers potentially associated with MS disease activity endpoints identified from prior studies. We trained machine learning (ML) models (Least Absolute Shrinkage and Selection Operator regression [LASSO], Random Forest, Extreme Gradient Boosting, Support Vector Machines, stacking ensemble learning, and stacking classification) for predicting Patient Determined Disease Steps (PDDS) score as the primary endpoint and reported model performance using the held-out test set. The study included 431 participants (mean age 49 years, 81% women, 94% non-Hispanic White). For binary PDDS score, combined feature input of routine clinical factors and the 19 proteins consistently outperformed base models (comprising clinical features alone or clinical features plus one single protein at a time) in predicting severe (PDDS ≥ 4) versus mild/moderate (PDDS < 4) disability across multiple machine learning approaches, with LASSO achieving the best area under the curve (AUCPDDS = 0.91) and other metrics. For ordinal PDDS score, LASSO model comprising combined clinical factors and 19 proteins as feature input (R2PDDS = 0.31) again outperformed base models. The two best-performing LASSO models (i.e., binary and ordinal PDDS score) shared six clinical features (age, sex, race/ethnicity, disease subtype, disease duration, DMT efficacy) and nine proteins (cluster of differentiation 6, CUB-domain-containing protein 1, contactin-2, interleukin-12 subunit-beta, neurofilament light chain [NfL], protogenin, serpin family A member 9, tumor necrosis factor superfamily member 13B, versican). By comparison, LASSO models with clinical features plus one single protein at a time as feature input did not select either NfL or glial fibrillary acidic protein (GFAP) as a final feature. Forcing either NfL or GFAP as a single protein feature into models did not improve performance beyond clinical features alone. Stacking classification model using five functional pathways to represent multiple proteins as meta-features implicated those involved in neuroaxonal integrity as significant contributors to predictive performance. Thus, serum multi-protein biomarker profiles improve the prediction of real-world MS disability status beyond clinical profile alone or clinical profile plus single protein biomarker, reaching clinically actionable performance.

PC71BM as Morphology Regulator for Highly Efficient Ternary Organic Solar Cells with Bulk Heterojunction or Layer-by-Layer Configuration.

The ternary strategy is one of the effective methods to regulate the morphology of the active layer in organic solar cells (OSCs). In this work, the ternary OSCs with bulk heterojunction (BHJ) or layer-by-layer (LbL) active layers are prepared by using the polymer donor PM6 and the non-fullerene acceptor L8-BO as the main system and the fullerene acceptor PC71BM as the third component. The power conversion efficiencies (PCEs) of BHJ OSCs and LbL OSCs are increased from 17.10% to 18.02% and from 17.20% to 18.20% by introducing PC71BM into the binary active layer, respectively. The in situ UV-vis absorption spectra indicate that the molecular aggregation and crystallization process can be prolonged by introducing PC71BM into the PM6:L8-BO or PM6/L8-BO active layer. The molecular orientation and molecular crystallinity in the active layer are optimized by introducing the PC71BM into the binary BHJ or LbL active layers, which can be confirmed by the experimental results of grazing incidence wide-angle X-ray scattering. This study demonstrates that the third component PC71BM can be used as a morphology regulator to regulate the morphology of BHJ or LbL active layers, thus effectively improving the performance of BHJ and LbL OSCs.

Hot-Casting Strategy Empowers High-Boiling Solvent-Processed Organic Solar Cells with Over 18.5% Efficiency.

Most top-rank organic solar cells (OSCs) are manufactured by the halogenated solvent chloroform, which possesses a narrow processing window due to its low-boiling point. Herein, based on two high-boiling solvents, halogenated solvent chlorobenzene (CB) and non-halogenated green solvent ortho-xylene (OX), preparing active layers with the hot solution is put forward to enhance the performance of the OSCs. In situ test and morphological characterization clarify that the hot-casting strategy assists in the fast and synchronous molecular assembly of both donor and acceptor in the active layer, contributing to preferable donor/acceptor ratio, vertical phase separation, and molecular stacking, which is beneficial to charge generation and extraction. Based on the PM6:BO-4Cl, the hot-casting OSCs with a wide processing window achieve efficiencies of 18.03% in CB and 18.12% in OX, which are much higher than the devices processed with room temperature solution. Moreover, the hot-casting devices with PM6:BTP-eC9 deliver a remarkable fill factor of 80.31% and efficiency of 18.52% in OX, representing the record value among binary devices with green solvent. This work demonstrates a facile strategy to manipulate the molecular distribution and arrangement for boosting the efficiency of OSCs with high-boiling solvents.

Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)-derived from exons 2-6 of EYA3-facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions. METHODS: CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model. RESULTS: CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells. CONCLUSIONS: Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

A Functional Stent Encapsulating Radionuclide in Temperature-Memory Spiral Tubes for Malignant Stenosis of Esophageal Cancer.

Stent implantation is a commonly used palliative treatment for alleviating stenosis in advanced esophageal cancer. However, tissue proliferation induced by stent implantation and continuous tumor growth can easily lead to restenosis. Therefore, functional stents are required to relieve stenosis while inhibiting tissue proliferation and tumor growth, thereby extending the patency. Currently, no ideal functional stents are available. Here, iodine-125 (125 I) nuclides are encapsulated into a nickel-titanium alloy (NiTi) tube to develop a novel temperature-memory spiral radionuclide stent (TSRS). It has the characteristics of temperature-memory, no cold regions at the end of the stent, and a uniform spatial dose distribution. Cell-viability experiments reveal that the TSRS can reduce the proliferation of fibroblasts and tumor cells. TSRS implantation is feasible and safe, has no significant systemic radiotoxicity, and can inhibit in-stent and edge stenosis caused by stent-induced tissue proliferation in healthy rabbits. Moreover, TSRS can improve malignant stenosis and luminal patency resulting from continuous tumor growth in a VX2 esophageal cancer model. As a functional stent, the TSRS combines the excellent properties of NiTi with brachytherapy of the 125 I nuclide and will make significant contributions to the treatment of malignant esophageal stenosis.

Identification of aneuploidy-related gene signature to predict survival in head and neck squamous cell carcinomas.

BACKGROUND: To parse the characteristics of aneuploidy related riskscore (ARS) model in head and neck squamous cell carcinomas (HNSC) and their predictive ability on patient prognosis. METHODS: Molecular subtyping of HNSC specimens was clustered by Copy Number Variation (CNV) data from The Cancer Genome Atlas (TCGA) dataset applying consistent clustering, followed by immune condition evaluation, differentially expressed genes (DEGs) analysis and DEGs function annotation. Weighted gene co-expression network analysis (WGCNA), protein-protein interaction, Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analysis were implemented to construct an ARS model. A nomogram for clinic practice was designed by rms package. Immunotherapy evaluation and drug sensitivity prediction were also carried out. RESULTS: We stratified HNSC patients into three different molecular subgroups, with the best prognosis in C1 cluster among 3 clusters. C1 cluster displayed greatest immune infiltration status. The most DEGs between C1 and C2 groups, mainly enriched in cell cycle and immune function. We constructed a nine-gene ARS model (ICOS, IL21R, CCR7, SELL, CYTIP, ZAP70, CCR4, S1PR4 and CD79A) that effectively differentiates between high- and low-risk patients. Patients in low ARS group showed a higher sensitivity to immunotherapy. A nomogram built by integrating ARS and clinic-pathological characteristics helped predict clinic survival benefit. Drug sensitivity evaluation found that 4/9 inhibitor drugs (MK-8776, AZD5438, PD-0332991, PHA-665752) acted on the cell cycle. CONCLUSIONS: We classified 3 molecular subtypes for HNSC patients and established an ARS prognostic model, which offered a prospective direction for prognosis in HNSC.

Iodine-125 seed implantation in the treatment of malignant tumors.

Malignant tumors are major causes of morbidity and mortality in China. Despite advances in surgical, radiological, chemotherapeutic, molecular targeting, and immunotherapeutic treatments, patients with malignant tumors still have poor prognoses. Low-dose-rate brachytherapy, specifically 125I seed implantation, is beneficial because of its high local delivery dose and minimal damage to surrounding tissues. Consequently, it has gained increasing acceptance as a treatment modality for various malignant tumors. In this study, we explored the fundamental principles, clinical applications, and new technologies associated with 125I radioactive seed implantation.

Enrichment of anchoring sites by introducing supramolecular halogen bonds for the efficient perovskite nanocrystal LEDs.

Considering the multi-functionalization of ligands, it is crucial for ligand molecular design to reveal the landscape of anchoring sites. Here, a typical triphenylphosphine (TPP) ligand was employed to explore its effect on the surface of CsPbI3 perovskite nanocrystals (PNCs). Except for the conventionally considered P-Pb coordination, an P-I supramolecular halogen bonding was also found on the NC surface. The coexistence of the above two types of bonding significantly increased the formation energy of iodine vacancy defects and improved the photoluminescence quantum yield of PNCs up to 93%. Meanwhile, the direct interaction of P and I enhanced the stability of the Pb-I octahedra and dramatically inhibited the migration of I ions. Furthermore, the introduction of additional benzene rings (2-(Diphenylphosphino)-biphenyl (DPB)) increased the delocalized properties of the PNC surface and significantly improved the charge transport of the PNCs. As a result, the DPB passivated CsPbI3 NCs based top-emitting LEDs exhibite a peak external quantum efficiency (EQE) of 22.8%, a maximum luminance of 15, 204 cd m-2, and an extremely low-efficiency roll-off of 2.6% at the current density of 500 mA cm-2.

Systemic Mutation of Ncf1 Ameliorates Obstruction-Induced Renal Fibrosis While Macrophage-Rescued NCF1 Further Alleviates Renal Fibrosis.

Aims: NCF1, a subunit of the NADPH oxidase 2 (NOX2), first described the expression in neutrophils and macrophages and participated in the pathogenesis from various systems. However, there are controversial findings on the role of NCF1 in different kinds of kidney diseases. In this study, we aim to pinpoint the specific role of NCF1 in the progression of renal fibrosis induced by obstruction. Results: In this study, NCF1 expression was upregulated in kidney biopsies of chronic kidney disease patients. The expression level of all subunits of the NOX2 complex was also significantly increased in the unilateral ureteral obstruction (UUO) kidney. Then, we used wild-type mice and Ncf1 mutant mice (Ncf1m1j mice) to perform UUO-induced renal fibrosis. Results demonstrated that Ncf1m1j mice exhibited mild renal fibrosis but increased macrophages count and CD11b+Ly6Chi macrophage proportion. Next, we compared the renal fibrosis degree between Ncf1m1j mice and Ncf1 macrophage-rescued mice (Ncf1m1j.Ncf1Tg-CD68 mice). We found that rescuing NCF1 expression in macrophages further alleviated renal fibrosis and decreased macrophage infiltration in the UUO kidney. In addition, flow cytometry data showed fewer CD11b+Ly6Chi macrophages in the kidney of the Ncf1m1j.Ncf1Tg-CD68 group than the Ncf1m1j group. Innovation: We first used the Ncf1m1j mice and Ncf1m1j.Ncf1Tg-CD68 mice to detect the role of NCF1 in the pathological process of renal fibrosis induced by obstruction. Also, we found that NCF1 expressed in different cell types exerts opposing effects on obstructive nephropathy. Conclusion: Taken together, our findings support that systemic mutation of Ncf1 ameliorates renal fibrosis induced by obstruction, and rescuing NCF1 in macrophages further alleviates renal fibrosis.

Clinical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis.

An 18-protein multiple sclerosis (MS) disease activity (DA) test was validated based on associations between algorithm scores and clinical/radiographic assessments (N = 614 serum samples; Train [n = 426; algorithm development] and Test [n = 188; evaluation] subsets). The multi-protein model was trained based on presence/absence of gadolinium-positive (Gd+) lesions and was also strongly associated with new/enlarging T2 lesions, and active versus stable disease (composite of radiographic and clinical evidence of DA) with improved performance (p < 0.05) compared to the neurofilament light single protein model. The odds of having ≥1 Gd+ lesions with a moderate/high DA score were 4.49 times that of a low DA score, and the odds of having ≥2 Gd+ lesions with a high DA score were 20.99 times that of a low/moderate DA score. The MSDA Test was clinically validated with improved performance compared to the top-performing single-protein model and can serve as a quantitative tool to enhance the care of MS patients.

Inhibitory Effect of Tea Saponin on Major Apple-Disease-Inducing Fungi.

Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.